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Biomedical subjects

J Baron

Publications and source records attributed to J Baron.

At least 109 records · Page 6Linked to original sources

Linear growth in the rabbit is continuous, not saltatory.

A recent report in Science suggests that human growth occurs in brief bursts, up to 1.65 cm in a single day, separated by extended periods of stasis, lasting up to 63 days. Thus, the organism is proposed to alternate between two states, one with a growth velocity of zero, the other with a mean annualized growth velocity greater than 350 cm/yr. These observations, if correct, suggest the existence of a previously unsuspected hormonal mechanism capable of abruptly switching growth plate cell division on and off and of synchronizing cellular growth not only throughout the growth plate, but presumably throughout all the growth plates in the organism. However, the experimental assessment of short-term growth velocity in the human faces the formidable obstacle of a technical error of measurement that exceeds the mean daily growth rate. Accordingly, we tested the saltatory growth hypothesis by measuring proximal tibial growth in the rabbit, a model in which daily growth rate could be measured more than 15 times more accurately than in the human. The model of saltation and stasis predicts a majority of daily growth velocities clustered around zero, and a minority of high growth velocities, that is, a bimodal distribution. The frequency distribution of observed daily growth velocities instead approximated a single Gaussian distribution, indicating continuous growth. We conclude that linear growth, in the most accurate mammalian system yet studied, is continuous, not saltatory.

Animals↗

Dexamethasone increases growth hormone receptor messenger ribonucleic acid levels in liver and growth plate.

Glucocorticoid inhibits linear growth and renders target tissues, particularly liver and growth plate, insensitive to GH. We hypothesized that glucocorticoid-induced GH insensitivity is due to decreased gene expression of the GH receptor at the messenger RNA (mRNA) level. To test this hypothesis, we treated 4.5-wk-old male rabbits (n = 6-9 per group) with ip dexamethasone or vehicle and measured GH receptor mRNA levels (by RNase protection assay) and serum GH-binding protein levels (by radioimmunoprecipitation assay). Contrary to our hypothesis, dexamethasone administered in growth-suppressing doses did not decrease GH receptor mRNA levels in liver or growth plate. Instead a tissue-specific stimulation of GH receptor mRNA levels was observed. The dose-response relationship of this effect was biphasic, since the lower growth-suppressing dose of dexamethasone (0.1 mg/kg.day) caused the greater increase in GH receptor mRNA levels, whereas the higher growth-suppressing dose (4 mg/kg.day) had less effect. The dexamethasone-induced increase in GH receptor mRNA was observed in growth plate and liver, target tissues important for linear growth, but not in kidney. Serum GH-binding protein levels also showed a stimulatory response to dexamethasone treatment, with a biphasic dose-response relationship. These data suggest that glucocorticoid-induced GH insensitivity cannot be explained by decreased GH receptor mRNA levels. To the contrary, dexamethasone causes a tissue-specific stimulation in GH receptor mRNA levels with a biphasic dose-response relationship.

Animals↗

Catch-up growth after glucocorticoid excess: a mechanism intrinsic to the growth plate.

In humans and other mammals, the release from growth-inhibiting conditions, such as glucocorticoid excess, leads to supranormal linear growth. The prevailing explanation for this catch-up growth involves a central nervous system mechanism that compares actual body size to an age-appropriate set-point and adjusts growth rate accordingly via a circulating factor. Although such a neuroendocrine "sizostat" was hypothesized more than 30 yr ago, its existence has never been confirmed experimentally. Here we show that suppression of growth within a single growth plate by locally administered glucocorticoid is followed by local catch-up growth that is restricted to the affected growth plate. Thus, the catch-up growth cannot be explained by neuroendocrine mechanism but, rather, must arise from a mechanism intrinsic to the growth plate. To explain this finding, we propose that the normal senescent decline in growth plate function depends not on age per se, but on the cumulative number of stem cell divisions, and that glucocorticoid administration, by suppressing stem cell proliferation, delays senescence, resulting in catch-up growth after the growth-inhibiting agent is removed.

Aging↗

Induction of growth plate cartilage ossification by basic fibroblast growth factor.

In mammals, longitudinal bone growth results from the precise coupling of chondrogenesis and osteogenesis within the epiphyseal growth plate, a process termed endochondral ossification. The mechanisms coupling chondrogenesis and osteogenesis are unknown. Previous studies have shown that both basic fibroblast growth factor (bFGF) and acidic FGF are expressed by growth plate chondrocytes. Here we show that bFGF, infused directly into the rabbit proximal tibial growth plate, accelerates vascular invasion and ossification of growth plate cartilage. Our results suggest the possibility that bFGF (or a related member of the FGF family) couples osteogenesis to chondrogenesis by attracting vascular and bone cell invasion from the adjacent metaphyseal bone.

Animals↗

Technetium 99m-MDP scintigraphy of patients undergoing implant prosthetic procedures: a follow-up study.

The clinical evaluation of peri-implant tissue is mainly based on x-rays. In recent years, radioisotope scintigraphy using Tc-99m-MDP (technetium-99m-methylene diphosphonate) proved to be a useful and reliable clinical method for measuring increased metabolic activity at specific sites of the skeletal tissue. Twenty-six (26) patients (26 to 75 years) who were diagnosed for implant prosthetic treatment modality were randomly chosen to participate in this study. Each patient was injected with 20 mCi of Tc-99m-MDP was scanned 2 hours later by gamma-camera for isotope uptake levels in the jaws. Each patient was scanned 1 to 4 times, starting 2 weeks after implant surgery and up to the 40th week postsurgery. Blade and screw type implants using the non-submerged, one-stage technique were placed. Therefore, the prosthetic reconstruction was initiated 2 weeks after implant surgery. In order to compare the different scans we formulated a relative "bone scan index" (BSI). The results of 62 scans were plotted as BSI against time after implant surgery. A mathematical regression analysis of the BSI was also performed. At the initial stage of 2 to 3 weeks after surgery the BSI is high and then gradually declines. While BSI of the implants in the mandible reaches baseline levels after 12 weeks, the BSI in the maxilla reaches baseline only after 20 weeks. On the other hand, there was no difference in BSI with regard to blade or screw type implant. Here we were able to demonstrate that the process is independent of implant modality and depends on the specific metabolic properties of the jaw.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Primary and secondary ovarian hypoplasia].

In 98 young women with lack of maturity, with menstrual disturbances and with insufficiency of the primary and secondary sexual signs an the basis of clinical and hormonal investigations in 61.2% the primary and in 38.8% the secondary ovarian hypoplasia was established. This allowed in spite of great clinical resemblance of the investigated persons to the proper diagnosis and to the choice of the suitable therapy.

Adult↗

On the use of ambulatory blood pressure recordings and insulin sensitivity measurements in support of the insulin-hypertension hypothesis.

OBJECTIVE: To determine the possible correlations between ambulatory blood pressure and insulin sensitivity, compared with correlations between office blood pressure and insulin. DESIGN: Observational study. SETTING: Policlinic at the Department of Geriatrics, Uppsala, Sweden. PATIENTS: Caucasian patients (n = 149) of both sexes with untreated essential hypertension. MAIN OUTCOME MEASURES: The hyperinsulinaemic euglycaemic clamp and office blood pressure in all subjects. In subgroups, also the oral glucose-tolerance test (n = 96) and 24-h ambulatory blood pressure (n = 84). RESULTS: Significant correlations were seen between the insulin sensitivity index and ambulatory blood pressure recordings, whereas fasting plasma insulin levels were uncorrelated with office blood pressure. The insulin sum and the 2-h insulin level of the oral glucose-tolerance test were more closely correlated with ambulatory blood pressure recordings than was the fasting insulin level. In multiple regression analyses the night-time diastolic blood pressure showed a significant correlation with the insulin sensitivity index even after controlling for the effects of sex, age and body mass index. CONCLUSION: The apparent association between blood pressure and insulin resistance not only is obscured by measurement error, but is also affected by the particular measures of insulin resistance and blood pressure used. The present study provides further evidence that a relationship exists between blood pressure and hyperinsulinaemia or insulin resistance.

Blood Pressure↗

[Cystic hepatic malignant tumors].

Non-parasitic hepatic cysts are common finding at abdominal sonography and in vast majority they are benign lesions. We report two cases of cystic liver neoplasms, namely the biliary cystadenocarcinoma and malignant hemangioendothelioma. In both cases, despite slow development of the tumour the presence of cyst considerably delayed diagnosis and hindered surgical treatment. We believe that more aggressive approach in "atypical" hepatic cysts could improve prognosis in such cases.

Adult↗

[Angiomatosis of the liver].

Cavernous haemangioma of the liver is the most frequently observed benign hepatic tumour. Polyangiomatosis is a great rarity, and in view of the similarity to metastatic tumours, it is a serious diagnostic problem. In the paper three cases are described of polyangiomatosis of the liver diagnosed on the basis of abdominal ultrasonography. Final diagnosis was made analysing USG, CT, scintigraphy with labelled erythrocytes, and laparoscopy. In all described cases, despite significant enlargement of the liver containing multiple hemangiomas, no features indicating liver damage were found in the laboratory investigations. This seems to be an important diagnostic indicator in the diagnosis of this disease.

Adult↗

[Diagnosis and treatment of congenital adrenal hyperplasia in women].

In 32 women with signs of androgenization, menstrual disturbances and distinct elevated values of 17-KS, DHEA, pregnantriole, testosterone and very reduced level of 17-OHCS congenital adrenal hyperplasia was diagnosed which established 12.5% individuals with intersexualism. The method of conservative or/and operative treatment and the prognosis were discussed.

17-Hydroxycorticosteroids↗

[Partial androgen insensitivity syndrome].

There were studied 13 individuals with partial androgen insensitivity syndrome (PAIS) and we observed hypertrophy of clitoris in 92.3%, female pubic hair in 69.2%, complete absence of vagina in 69.2% and normal female development of breasts in 38.5%. In the partial form of AIS more frequent than in the complete form surgery for inguinal hernia, for hypertrophy of clitoris and for artificial vagina was necessary. The discussed form of this male hermaphroditism is caused by rare and untypical mutations in the androgen receptor gene and a differential diagnosis must be performed by exclusion above all the anorchism, Mayer-Rokitansky-Küstner syndrome and congenital adrenal hypertrophy. Among all cases of AIS the frequency of PAIS appeared 28.3%.

Adolescent↗

[New aspects in diagnosis and therapy of Turner's syndrome].

In the last 35 years we noticed 91 cases of Turner's syndrome. To the obligatory symptoms of the syndrome belong primary amenorrhoea, sexual infantilism, elevated values only of FSH and very reduced levels of estrogens, chromosomal aberrations in karyotype, most often 45, X and presence of streak gonads. The facultative symptoms of the syndrome belong short stature (94.5% of patients), presence of congenital defects (short webbed neck in 44.4%) and sterility (98.9%). Therapy above 15 years excepting to cause the menstrual cycles have to development the second sexual symptoms by giving enough large doses of oestrogens and gestagens. The best effects we obtain nearly in 100% in the development of breasts, in slowly growth of sexual hair and in the growth of the stature which does not cross the height of 150 cm and only in six patients attained in average 152.5 cm.

Adolescent↗

[Classical and incomplete androgen insensitivity syndromes].

On the basis of investigation and observation of 41 individuals with androgen insensitivity syndrome (AIS) author confirms that at the phenotypic female and genotypic male patients the value of testosterone in plasma is 6.4 +/- 1.6 mg/ml, corresponding to that characteristic to healthy males. In the classical form there is absent or very scarce pubic hair in 100%, normal development of breasts in 97% of cases, blind vagina of mean length 5.0 +/- 2.3 cm in 97% of cases and inguinal hernia in 30% of cases. In the incomplete form of AIS normal breasts occurs in 62.5%, public hair in 50%, complete absence of vagina in 62.5%, blind vagina of mean length 2.5 cm in 37.5%, inguinal hernia in 75% and hypertrophy of clitoris of mean length 2.0 +/- 1.0 cm in 62.5%, what distinguishes this form of the syndrome from classical form. In incomplete form surgery for inguinal hernia in 87.5% is necessary. In 37.5% artificial vagina has to be created. Classical form occurs in 80.5% and incomplete form in 19.5%. The malignity of the gonads in the discussed syndrome is rare. Castration should be avoided before the patient attains full sexual maturity. Normal value at testosterone level characteristic for men suggests that the lack of sensitivity to androgens of the target cells is the main cause of the disease and is definitively caused by mutations in the androgen receptor gene.

Adolescent↗

Diet and risk of gastric cancer. A population-based case-control study in Sweden.

A case-control study to evaluate risk factors of gastric cancer was carried out in areas with contrasting incidence rates in Sweden. Face-to-face interviews were conducted with 338 of 456 eligible histologically confirmed gastric-cancer cases and 669 of 880 eligible control subjects, sampled from population registers and frequency-matched by age and gender. We focused on 2 periods, adolescence and 20 years prior to interview. The association of gastric-cancer risk with dietary habits during adolescence were similar to that found for the period 20 years before interview; high consumption of wholemeal bread, fruit and vegetables was associated with reduced gastric-cancer risk. In addition, cheese, fish and tea had a protective effect during adolescence. Increased gastric-cancer risk was related to whole-milk consumption, but this association decreased substantially in a multivariate analysis including vegetables. There was a positive relationship between gastric-cancer risk and the age at which the interviewees started using refrigerators. This population-based study confirmed the protective effect of a high consumption of vegetables and fruit in the development of gastric cancer, but failed to find any association between intake of meat, sausage, cold cuts, liver, salt, coffee, the habit of frying, smoking or grilling foods, and risk of gastric cancer.

Adult↗

Increasing cancer risk in younger birth cohorts in Sweden.

There is controversy about cancer mortality trends; some analyses show increasing mortality, but others suggest that rates are falling in the youngest age groups. We have investigated trends in cancer incidence in the whole of Sweden for the period 1958 to 1987. 837,085 cancer cases were registered during the period studied. Incidence rate patterns were studied by age-period-cohort modelling. The risk of cancer was higher for people born during the 1950s than for those born in 1873-82; for women the risk was doubled and for men it was trebled. Although the rate of increase slowed, it showed no sign of levelling off in the youngest birth cohorts. The frequency of smoking-related cancers increased greatly in both sexes, but such tumours could explain only part of the rise in total cancer. These trends predict a continuing rise in the incidence rate of cancer, and suggest a worrying pattern of increasing population exposure to carcinogenic influences.

Adult↗

Localization and induction of cytochrome P450 1A1 and aryl hydrocarbon hydroxylase activity in rat nasal mucosa.

Cytochrome P450 1A1 was localized immunohistochemically and benzo[a]pyrene hydroxylase activity was identified in situ by means of fluorescence histochemistry in the nasal mucosa of untreated, 3-methylcholanthrene-treated or Aroclor 1254-treated rats. Cytochrome P450 1A1 was localized predominantly within Bowman's glands, with considerably less staining occurring in the olfactory epithelium of untreated rats. Similarly, benzo[a]pyrene was hydroxylated to the greatest extent in Bowman's glands and, to a lesser extent, in olfactory epithelial cells. Pre-treatment of tissue sections of nasal mucosa with anti-P450 1A1 inhibited most of the benzo[a]pyrene hydroxylase activity present. Although 3-methylcholanthrene treatment did not affect either cytochrome P450 1A1 or hydroxylase activity in the nasal mucosa, a single intraperitoneal injection of Aroclor 1254 significantly increased anti-P450 1A1 binding in Bowman's glands and in the olfactory and respiratory epithelia, and dramatically enhanced benzo[a]pyrene hydroxylase activity in the epithelia and the subepithelial ducts and glands in both the olfactory and respiratory regions. In contrast to its effects on cytochrome P450 1A1, Aroclor 1254 produced a considerably greater induction of hydroxylase activity in the respiratory region, especially in the seromucous glands, than in the olfactory region. These results suggest that Aroclor 1254 treatment also induces other forms of cytochrome P450 in the respiratory region of the nasal mucosa.

Animals↗

[Androgen insensitivity syndrome. Clinical and endocrinologic study of 40 cases].

It was found on the basis of observation of 40 patients with androgen insensitivity syndrome carried out during over 25 years that in patients with female phenotype and male genotype the mean blood plasma level of testosterone was 6.4 +/- 1.6 ng/ml, corresponding to that characteristic for healthy males. In classical form of the syndrome there is absent or very scarce pubic hair in 100% of cases, normal development of mammary glands in 97% of cases, blind vagina of mean length 5.0 +/- 2.3 cm in 97% of cases and unilateral or bilateral inguinal hernia in 30.3% of cases. In the incomplete form of androgen insensitivity normal development of mammary glands occurs in 71.4%, pubic hair in 57.1%, complete absence of vagina in 57.1%, blind vagina of mean length 2.5 cm in 42.9%, inguinal hernia in 71.4% and hypertrophy of clitoris of mean length 2.0 +/- 1.0 cm in 57.1% of cases, what distinguishes this form of the syndrome from classical form. In 85.7% of cases of incomplete form surgery for inguinal hernia is necessary; in 42.9% artificial vagina has to be created. Among the patients with the syndrome, classical form occurs in 82.5% and incomplete form in 17.5% of cases. Distinguishing between the two forms is fully justified because of clinical and therapeutic reasons. Though malignancy of the gonads appears infrequently among the patients with the insensitivity syndrome, but periodical control of the state of testes, especially at adulthood is necessary. Castration should be avoided before the patient attains full sexual maturity. Normal value of testosterone level, characteristic for men, suggests that lack of sensitivity to androgens of the target cells is the main cause of the disease.

Adult↗